Parallel CRISPR-Cas9 screens identify mechanisms of PLIN2 and lipid droplet regulation.

Despite the key roles of perilipin-2 (PLIN2) in governing lipid droplet (LD) metabolism, the mechanisms that regulate PLIN2 levels remain incompletely understood. Here, we leverage a set of genome-edited human PLIN2 reporter cell lines in a series of CRISPR-Cas9 loss-of-function screens, identifying genetic modifiers that influence PLIN2 expression and post-translational stability under different metabolic conditions and in different cell types. These regulators include canonical genes that control lipid metabolism as well as genes involved in ubiquitination, transcription, and mitochondrial function.

Identification and prediction of Parkinson's disease subtypes and progression using machine learning in two cohorts.

The clinical manifestations of Parkinson's disease (PD) are characterized by heterogeneity in age at onset, disease duration, rate of progression, and the constellation of motor versus non-motor features. There is an unmet need for the characterization of distinct disease subtypes as well as improved, individualized predictions of the disease course. We used unsupervised and supervised machine learning methods on comprehensive, longitudinal clinical data from the Parkinson's Disease Progression Marker Initiative (n = 294 cases) to identify patient subtypes and to predict disease progression.

A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states.

Microglia are emerging as key drivers of neurological diseases. However, we lack a systematic understanding of the underlying mechanisms. Here, we present a screening platform to systematically elucidate functional consequences of genetic perturbations in human induced pluripotent stem cell-derived microglia.

Multi-modality machine learning predicting Parkinson's disease.

Personalized medicine promises individualized disease prediction and treatment. The convergence of machine learning (ML) and available multimodal data is key moving forward. We build upon previous work to deliver multimodal predictions of Parkinson's disease (PD) risk and systematically develop a model using GenoML, an automated ML package, to make improved multi-omic predictions of PD, validated in an external cohort.

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis.

Single-cell transcriptomics provide a systematic map of gene expression in different human cell types. The next challenge is to systematically understand cell-type-specific gene function. The integration of CRISPR-based functional genomics and stem cell technology enables the scalable interrogation of gene function in differentiated human cells.

Herpes simplex virus encephalitis in hamadan, iran.

Background And Objectives: Encephalitis can cause a severe public health problem. The main aim of this research was to evaluate the medical laboratory results of patients with Herpes Simplex Virus (HSV) encephalitis.

Materials And Methods: Diagnosis of encephalitis for these patients was firstly based on a clinical profile for Herpes Simplex Encephalitis (HSE), plus either a detected HSV1&2-DNA by PCR in CSF or brain neuro-imaging results.

Celiac disease in patients with chronic psychiatric disorders.

Aim: The aim of this study was to determine the prevalence of celiac disease in Iranian patients suffering from chronic depression or schizophrenia.

Background: Psychiatric disorders are common in untreated celiac disease.

Patients And Methods: Two hundred Iranian inpatient men with in chronic phase of depressive disorders or schizophrenia, and 200 age-matched healthy male subjects were screened for celiac disease by anti-tissue transglutaminase IgA antibodies.

The personality trait openness is related to cerebral 5-HTT levels.

Potentiation of serotonergic transmission increases cognitive flexibility, but can in other circumstances increase sensitivity to stressful environmental cues. The personality trait Openness to Experience reflects and is also associated with an increased risk for mood disorders. We hypothesized that the personality trait has an association with a biomarker of serotonergic transmission, the plasma membrane serotonin transporter (5-HTT).

The sodium pump Ena1p provides mechanistic insight into the salt sensitivity of vacuolar protein sorting mutants.

The vacuolar/endosomal network has an important but as yet undefined role in the cellular tolerance to salt stress. We hypothesized that the mechanistic basis for the importance of vacuolar protein sorting (vps) components in salt tolerance is the targeting of the crucial sodium exporter Ena1p to the plasma membrane. The link between Ena1p and the vps components was established by the observation that overexpression of Ena1p could suppress the salt sensitivity of the ESCRT knockouts vps20Delta, snf7/vps32Delta and snf8/vps22Delta.

Comparative proteomics of industrial lager yeast reveals differential expression of the cerevisiae and non-cerevisiae parts of their genomes.

The proteomes of three industrial lager beer strains, CMBS33, OG2252 and A15, were analysed under standardised laboratory growth conditions. Protein spots in the 2-DE pattern of the lager strains were subjected to MS/MS to identify protein variants. We found the protein composition of the three lager strains to be qualitatively rather similar, while being substantially different from the Saccharomyces cerevisiae strain BY4742.

E-selectin S128R polymorphism leads to severe asthma.

The E-selectin mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of asthma. It has been suggested that an S/R (Serine128Arginine) polymorphism of E-selectin alters ligand binding function. Our purpose in this study was to determine whether this Serine128Arginine polymorphism influences the risk of asthma and also to analyze the possible correlation of disease severity in Iranian patients with polymorphism of E-selection.

Senataxin, the yeast Sen1p orthologue: characterization of a unique protein in which recessive mutations cause ataxia and dominant mutations cause motor neuron disease.

A severe recessive cerebellar ataxia, Ataxia-Oculomotor Apraxia 2 (AOA2) and a juvenile onset form of dominant amyotrophic lateral sclerosis (ALS4) result from mutations of the Senataxin (SETX) gene. To begin characterization this disease protein, we developed a specific antibody to the DNA/RNA helicase domain of SETX. In murine brain, SETX concentrates in several regions, including cerebellum, hippocampus and olfactory bulb with a general neuronal expression profile, colocalizing with NeuN.

SIMPLE interacts with NEDD4 and TSG101: evidence for a role in lysosomal sorting and implications for Charcot-Marie-Tooth disease.

Mutation of the SIMPLE gene (small integral membrane protein of the lysosome/late endosome) is the molecular basis of Charcot-Marie-Tooth disease type 1C (CMT1C), a demyelinating peripheral neuropathy. Although the precise function of SIMPLE is unknown, prior reports suggest it localizes to the lysosome/late endosome. Furthermore, murine Simple interacts with Nedd4 (neural precursor cell expressed, developmentally downregulated 4), an E3 ubiquitin ligase that is important for regulating lysosomal degradation of plasma membrane proteins.

SSR2(a) receptor expression and adrenergic/cholinergic characteristics in differentiated SH-SY5Y cells.

Somatostatin (SS) is an inhibitory regulator of secretory and proliferative responses that activates a group of receptors in the plasma membrane termed SSR1-5. SSR2 is one of the most abundant SSR, which also is expressed in high numbers in many neuroendocrine tumor types. Here, we describe a study of the presence and intracellular localization of the spliced variant SSR2(a) and its endogenous ligand SS in the cultured human neuroblastoma (NB) cell line, SH-SY5Y, by immunohistochemistry and confocal laser scanning.

Adrenergic differentiation and SSR2a receptor expression in CAD-cells cultured in serum-free medium.

The CAD cell line originates from catecholaminergic neurons in the central nervous system (CNS) of a simian virus large T antigen transgenic mouse. In the present study, we have immunohistochemically characterized the cell line after differentiation in serum-free medium, using immunofluorescence in combination with confocal laser scanning microscopy (CLSM), immunoblot, and ribonuclease protection assay (RPA). Tyrosine hydroxylase (TH)-, phenylethanolamine-N-methyltransferase (PNMT)-, neuropeptide Y (NPY)-, vesicular monoamine transporter subtype 2-, vasoactive intestinal peptide (VIP)-, somatostatin (SS)-, synaptophysin-, synaptic vesicle protein 2 (SV2)-, and growth-associated protein of 43 (GAP-43)-immunoreactivities (IRs) were present in the cells but not choline acetyltransferase and vesicular acetylcholine transporter.

Indium-111-octreotide scintigraphy, intraoperative gamma-detector localisation and somatostatin receptor expression in primary human breast cancer.

12 women with primary breast cancer underwent somatostatin receptor scintigraphy (SRS) with 111In-DTPA-D-Phe1-octreotide. The tumour sizes varied between 2 and 5 cm and were all, except one, palpable at clinical examination. Tumour biopsies were taken with additional sampling from normal breast tissue, fat, muscle, axillary lymph nodes and peripheral blood.